The 49ers and Seahawks are No. 1 and No. 4, respectively, in the league in total defense. They are No. 3 and No. 2, respectively, in scoring defense. The 49ers are No. 2 against the pass; the Seahawks are No. 2 against the run.

The Seahawks come in with a confidence after rallying to beat one of last year's Super Bowl teams, the New England Patriots, and getting a season-best performance from rookie quarterback Russell Wilson.

The Niners will be angry having being routed by last year's other Super Bowl team, the New York Giants, at home and watching veteran quarterback Alex Smith have his worst game in three years.

Before Week 6, it looked like the Niners were the team to beat in the NFC. After Week 6, there's a bit of uncertainty whether they are the best in the NFC West. Here's a big chance, in prime time, to set both records straight.

The Seahawks were responsible for the Niners' only division loss a season ago, winning 19-17 in Seattle. But this year, the 'Hawks have already lost at Arizona and at St. Louis.

The difference is how Wilson has trouble protecting the ball on the road.

Wilson aced his three home games (116.9 passer rating, six touchdowns, no interceptions). Away from CenturyLink Field, he played a lot more like a rookie (60.3 rating, two TDs, six INTs). He figures to face a jacked-up crowd at Candlestick Park, creating the hostile environment.

The 49ers will first look to restore their run defense after being gashed by the Giants' Ahmad Bradshaw last week. Once they slow Marshawn Lynch — the first power back to pop into the end zone against them in 2011 — they can put Wilson in uncomfortable situations with their pass rush.

The challenge for Smith, coming off a three-interception game against the Giants, is to first go back what he's done best: protect the ball. The Seahawks have the secondary to bait him into more bad throws, and expect their front four to bring consistent pressure.

Patriots quarterback Tom Brady wasn't immune to mistakes against the Seahawks last week, throwing two interceptions that facilitated the Seahawks' fourth-quarter rally. The Niners must take the good that Brady did, however, and also follow what Seattle did with Wilson: Let Smith loose in an up-tempo passing attack.

Frank Gore and Kendall Hunter can't expect to find much running room, so Smith must make big pass plays to win. The Niners must get Michael Crabtree, Vernon Davis, Randy Moss and Mario Manningham on the field at the same time. There was too little of Moss, too late against the Giants.

The Seahawks' secondary is very good, but given how much attention the athletic Davis and Moss (still with good deep speed) can create downfield, it's on Crabtree and Manningham to produce against single coverage. Manningham played well against the Giants, but Crabtree can't have three catches for 26 yards again.

This is a critical game for Smith to prove the quarterback we saw in Week 5 against the Bills is the one who emerged in the past two seasons. He will be in position to make fewer miscues than Wilson and must take advantage.